Discovery of new thieno[2,3- d]pyrimidines as EGFR tyrosine kinase inhibitors for cancer treatment

  • Future Med Chem. 2023 Jul;15(13):1167-1184. doi: 10.4155/fmc-2023-0086.
Eman A Sobh  1 ,  Mohammed A Dahab  2 ,  Eslam B Elkaeed  3 ,  Aisha A Alsfouk  4 ,  Ibrahim M Ibrahim  5 ,  Ahmed M Metwaly  6  7 ,  Ibrahim H Eissa  2
Affiliations
  • 1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.
  • 2. Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
  • 3. Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi Arabia.
  • 4. Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, PO Box 84428, Riyadh, 11671, Saudi Arabia.
  • 5. Biophysics Department, Faculty of Science, Cairo University, Cairo, 12613, Egypt.
  • 6. Pharmacognosy & Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
  • 7. Biopharmaceutical Products Research Department, Genetic Engineering & Biotechnology Research Institute, City of Scientific Research & Technological Applications (SRTA-City), Alexandria, 21934, Egypt.
PMID: 37529910 DOI: 10.4155/fmc-2023-0086
Abstract

Background: EGFR has been considered a vital molecular target in Cancer management. Aim: The discovery of new thieno[2,3-d]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Methods: Nine derivatives were designed, synthesized and subjected to in vitro and in silico studies. Results: Compound 7a significantly inhibited the growth of HepG2 and PC3 cells for both EGFR wild-type and EGFRT790M. Compound 7a caused a significant apoptotic effect, arresting HepG2 cells' growth in the S and G2/M phases. Docking and molecular dynamics simulation studies confirmed the correct and stable binding modes of the synthesized compounds against the active sites. Conclusion: Compound 7a is a promising dual EGFR Inhibitor for Cancer treatment.

Keywords
EGFR TKIs; MD simulations; anticancer; docking; thieno[2,3-d]pyrimidine.
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